Alpha-peptide/beta-peptoid chimeras.

[structure: see text] We describe the synthesis and characterization of the first generation of oligomers consisting of alternating repeats of alpha-amino acids and chiral N-alkyl-beta-alanine (beta-peptoid) residues. These chimeras are stable toward proteolysis, non-hemolytic, and possess antibacterial activity comparable to well-known antimicrobial agents. Moreover, the chimeras exhibit length-dependent, concentration-dependent, solvent-dependent, and ion-strength-dependent ellipticity, indicating the presence of a secondary structure in solution. Thus, alpha-peptide/beta-peptoid oligomers represent a promising novel peptidomimetic backbone construct for biologically active ligands.

Acetylcholinesterase and butyrylcholinesterase inhibitory compounds from Corydalis cava Schweigg. & Kort.

In the course of screening plants used in Danish folk medicine as memory enhancers, a crude methanolic extract of tubers from Corydalis cava showed significant acetylcholinesterase inhibitory activity in a dose-dependent manner. Activity guided fractionation of the methanolic extract resulted in the isolation of three alkaloids, bulbocapnine (1), corydaline (2) and corydine (3) as active constituents. Bulbocapnine inhibited acetylcholinesterase as well as butyrylcholinesterase in a dose-dependent manner with IC(50) values of 40+/-2 microM and 83+/-3 microM, respectively. Corydaline inhibited acetylcholinesterase in a dose-dependent manner with an IC(50) value of 15+/-3 microM and corydine inhibited butyrylcholinesterase in a dose-dependent manner with an IC(50) value of 52+/-4 microM. Corydaline was considered inactive against butyrylcholinesterase and corydine against acetylcholinesterase, due to IC(50)>100 microM.

Antiplasmodial and GABA(A)-benzodiazepine receptor binding activities of five plants used in traditional medicine in Mali, West Africa.

Extracts of five medicinal plants: Boscia angustifolia, Cissus quadrangularis, Securidaca longipedunculata, Stylosanthes erecta and Trichilia emetica, used traditionally in Malian traditional medicine were screened for in vitro antiplasmodial activity and GABA(A)-benzodiazepine receptor binding activity. Four extracts showed significant antiplasmodial activities, with the dichloromethane extract of leaf of Securidaca longipedunculata being the most active (IC(50) of 7 microg/ml [95% CI: 5-9]). The dichloromethane extract of leaf of Trichilia emetica, in addition to its antiplasmodial activity (IC(50): 12 microg/ml [95% CI: 12-14]), exhibited a good binding activity to the GABA(A)-benzodiazepine receptor, while water and methanol extracts of the same plant did not show any activity. A strong GABA(A)-receptor complex binding activity was observed in the methanol extract of aerial part of Stylosanthes erecta. The results in this study justify some of the traditional indications of the plants investigated and may thus be candidates for Improved Traditional Medicines in Mali.

Screening of plants used in Danish folk medicine to treat memory dysfunction for acetylcholinesterase inhibitory activity.

Aqueous and methanolic extracts of 11 plants, used in Danish folk medicine for improvement of memory and cognition, and 3 Corydalis species were tested for acetylcholinesterase inhibitory activity using the Ellman colorimetric method. Significant inhibitory activity in dose-dependent manner was observed for extracts of Corydalis cava, Corydalis intermedia, Corydalis solida ssp. laxa and Corydalis solida ssp. slivenensis. Extracts of Ruta graveolens, Lavandula angustifolia, Rosmarinus officinalis, Petroselinum crispum and Mentha spicata exhibited moderate inhibition of the enzyme, defined as more than 15% at 0.1 mg/ml.

Screening of plants used in Danish folk medicine to treat epilepsy and convulsions.

Aqueous and ethanolic extracts of 42 plants used in Danish folk medicine for the treatment of epilepsy and convulsions, or for inducing sedation, were tested for affinity to the GABA(A)-benzodiazepine receptor in the flumazenil-binding assay. Ethanolic extracts of leaves of Primula elatior and Primula veris and aerial parts of Tanacetum parthenium exhibited good, dose-dependent affinity.

Ethnopharmacological evaluation of radal (leaves of Lomatia hirsuta) and isolation of 2-methoxyjuglone.

BACKGROUND: Leaves of Lomatia hirsuta are used in traditional medicine in Chile under the common name of "radal". A tea of radal is traditionally used for treatment of cough, bronchial troubles, and asthma. In a preliminary screening, extracts of the leaves revealed antifungal activity, and the present phytochemical study was undertaken to explain this activity and support the traditional use. METHODS: Along with the traditional tea, extracts of the leaves were screened for antifungal and toxic activities. The profile of secondary constituents was obtained using GC-MS. RESULTS: 2-Methoxyjuglone was isolated from the leaves of Lomatia hirsuta and found to be active against the pathogenic fungus Candida albicans (MIC = 8 microg/mL). Cinnamic acid and vanillic acid were identified as major constituents in the tea by GC-MS. The tea was found not to be toxic against Artemia salina. CONCLUSION: The presence of phenolic acids with antimicrobial properties supports the traditional use of Radal, and encourages further studies.

Methylenedioxy- and methoxyflavones from Melicope coodeana syn. Euodia simplex.

Three new natural products, 3,8-dimethoxy-5,7-dihydroxy-3',4'-methylenedioxyflavone, 3,6,8-trimethoxy-5,7-dihydroxy-3',4'-methylenedioxyflavone and 3,6,8,3',4'-pentamethoxy-5,7-dihydroxyflavone were isolated from Melicope coodeana syn. Euodia simplex (Rutaceae) along with 3,6,3'-trimethoxy-5,7,4'-trihydroxyflavone and 3,3'-dimethoxy-5,7,4'-trihydroxyflavone. The structural assignments are based on (1)H and (13)C NMR data, including discussion of the chemical shifts of C-2 in 3,5-dihydroxy- and 3-methoxy-5-hydroxyflavones. The presence of highly methoxylated and methylenedioxyflavones is characteristic of the genus Melicope, and the present findings support the recent transfer of Euodia simplex to Melicope.

Traditional medicine in Sakarya province (Turkey) and antimicrobial activities of selected species.

Traditional medicine in North-West of Turkey (Sakarya province) were studied during a 2 months field study by interviewing local informants from several villages. Plant species used to treat infections were tested for antimicrobial activity. Information was collected for 46 plant species from 30 families and for 5 animal species. Twenty four of the plant species were cultivated. Most used families were Asteraceae, Cucurbitaceae, Lamiaceae and Rosaceae and the most used plants were Artemisia absinthium, Equisetum telmateia, Lavandula stoechas, Melissa officinalis, Tussilago farfara and Urtica dioica. A total of 139 medicinal uses were obtained. Plants are used mainly for infectious diseases (18%), for neurological and psychological disorders (13.7%), cardiovascular disorders (13%), skin disorders (12.2%) and respiratory disorders (10.1%). Extracts were tested in vitro for antimicrobial activity against Staphylococcus aureus ATCC 65538, Staphylococcus epidermidis ATCC 12228, Escherichia coli ATCC 8739, Klebsiella pneumonia ATCC 4352, Pseudomonas aeruginosa ATCC 1539, Salmonella typhi, Shigella flexneri, Proteus mirabilis and Candida albicans ATCC 10231, using microbroth dilution technique according to National Committee for Clinical Laboratory Standards (NCCLS). This research showed that Arum maculatum, Datura stramonium, Geranium asphodeloides and Equisetum telmateia petroleum ether extracts had MIC values of 39.1 microg/ml, 78.1 microg/ml, 78.1 microg/ml and 39.1 microg/ml, respectively against Staphylococcus epidermidis. Datura stramonium petroleum ether extract had a MIC value of 39.1 microg/ml against Escherichia coli and Trachystemon orientalis ethanol extract had a MIC value of 39.1 microg/ml against Escherichia coli. The antimicrobial activity of Arum maculatum, Equisetum telmateia, Geranium asphodeloides, Plantago intermedia, Senecio vulgaris and Trachystemon orientalis has been reported here for the first time.

Screening of plants used in southern Africa for epilepsy and convulsions in the GABAA-benzodiazepine receptor assay.

A number of plants are traditionally used to treat mental diseases in South Africa. Aqueous and ethanol extracts of 43 plants that are traditionally used to treat against epilepsy and convulsions, were tested in the GABAA-benzodiazepine receptor binding assay, where the binding of 3H-Ro 15-1788 (flumazenil) to the benzodiazepine site is measured. The GABAA-benzodiazepine receptor complex is involved in epilepsy and convulsions. Out of the 118 extracts tested, one aqueous and 18 ethanol extracts showed activity. The most active extracts were the ethanolic leaf extracts of Rhus tridentata, Rhus rehmanniana and Hoslundia opposita and the ethanolic corm extract of Hypoxis colchicifolia, which all showed good dose-dependent activity.

Tea toxicity and cholinesterase inhibition of Huilliche herbal medicine.

Eleven species of Huilliche medicinal plants used traditionally against infections and for wound healing were tested for their cholinesterase inhibition activity. Two different teas (a 5-7 min infusion and a 1 h decoction, both in water) were tested for their toxicity against Artemia salina. The results from the present study clearly show that teas boiled for 1 h is much more toxic than teas infused for 5-7 min. These results support the different traditional use of the two teas, where the 1h tea is for external use only. Additionally, significant inhibition of cholinesterase has been observed for MeOH extracts of Acaena argentea, Amomyrtas meli and Pseudopanax laetevirens, with that of A. argentea being the most potent. All findings call for further investigations.

Screening of plants used in Danish folk medicine to treat depression and anxiety for affinity to the serotonin transporter and inhibition of MAO-A.

ETHNOPHARMACOLOGICAL RELEVANCE: A number of plant species are used in Danish folk medicine for treatment of depression and anxiety. MATERIALS AND METHODS: Aqueous and ethanolic extracts of 17 plant species were tested for affinity to the serotonin transporter and for inhibition of MAO-A-both targets for antidepressive treatment. RESULTS: An ethanolic extract of aerial parts of Borago officinalis had affinity to the serotonin transporter. Ten extracts, from eight plants, had IC(50) values below 25µg/ml extract in the MAO-A assay. The most active extracts in the MAO-A assay were the ethanol extract of seeds of Trigonella foenum-graecum (IC(50) 4µg/ml); ethanol extract of leaves of Apium graveolens (IC(50) 5µg/ml) and the water extract of aerial parts of Calluna vulgaris (IC(50) 8µg/ml). CONCLUSIONS: Besides Borago officinalis, which toxicity profile excludes it from further development as an herbal drug, none of the plants had potential as serotonin reuptake inhibitors. Several plants had MAO-A inhibitory activity.

Antimicrobial evaluation of Huilliche plant medicine used to treat wounds.

ETHNOPHARMACOLOGICAL RELEVANCE: The traditional use of 40 plant species used for treatment of wounds and associated infections by the Huilliche people of Chile was evaluated against bacterial and fungal human pathogens, especially including wound pathogens. MATERIALS AND METHODS: The extracts were tested against the fungi Penicillium expansum, Candida albicans and the bacteria Bacillus subtilis, Pseudomonas aeruginosa (four different strains), Staphylococcus aureus, Escherichia coli (four different strains), Streptococcus pneumoniae (four different strains with one being resistance to streptomycin). RESULTS: Thirteen of the plant species have interesting antimicrobial activities, with that of Acaena argentea, Aristotelia chilensis, Blechnum chilense, Francoa appendiculta, Gevuina avellana and Laureliopsis philippiana being the most noteworthy. CONCLUSIONS: The findings in the manuscript support the traditional use by the Huilliche people, and allow enhanced economical benefit and use by the locals. The results obtained on Acaena argentea, Aristotelia chilensis, Blechnum chilense, Francoa appendiculta, Gevuina avellana and Laureliopsis philippiana are of specific scientific interest, and further studies is needed in order to establish the active constituents of the species.

Targeted natural product isolation guided by HPLC-SPE-NMR: constituents of Hubertia species.

The hyphenated technique, high-performance liquid chromatography-solid-phase extraction-nuclear magnetic resonance spectroscopy (HPLC-SPE-NMR), has been applied for rapid identification of novel natural products in crude extracts of Hubertia ambavilla and Hubertia tomentosa. The technique allowed full or partial identification of all major extract constituents and demonstrated the presence of unusual quinic acid derivatives containing the (1-hydroxy-4-oxocyclohexa-2,5-dienyl)acetyl residue that exhibit strongly coupled ABXY patterns, the parameters of which were obtained by spin simulations. Using homo- and heteronuclear 2D NMR data acquired in the HPLC-SPE-NMR mode, complete structure determination of three new natural products, i.e., 3,5-di-O-caffeoyl-4-O-[(1-hydroxy-4-oxocyclohexa-2,5-dienyl)acetyl]quinic acid (1), its 2-hydroxy derivative (2), and 3,5-di-O-caffeoyl-4-O-[(4-hydroxyphenyl)acetyl]quinic acid (3), was performed. Finally, targeted isolation of 1 was achieved by SPE fractionation and preparative HPLC, followed by evaluation of its antioxidant and antimicrobial activity. In contrast to chlorogenic acid and 3,5-di-O-caffeoylquinic acid, which act as antioxidants, compound 1 proved at the same conditions to possess prooxidant activity in an assay evaluating the oxidation of human low-density lipoprotein induced by Cu(2+).

Antifungal constituents of Melicope borbonica.

Fractionation of extracts of the leaves of Melicope borbonica (syn. Euodia borbonica var. borbonica), a medicinal plant from the Réunion Island that is traditionally used for wound healing and other ailments, afforded an acetophenone (xanthoxylin) and two coumarins, scoparone and limettin, as the major constituents. All three compounds exhibited moderate antifungal activity against Candida albicans and Penicillium expansum, in accordance with the traditional use of the plant. Moreover, 2,4,6-trimethoxyacetophenone (methylxanthoxylin), three other coumarins [7-(3-methyl-2-butenyloxy)-6-methoxycoumarin, cedrelopsin and psoralen], two sesquiterpenes (alpha-curcumene and 3,6-epidioxy-1,10-bisaboladiene), eugenol, methyleugenol and a lignan (sesamin) were isolated. None of the isolated constituents exhibited antiin fl ammatory activity in vitro. No alkaloids were detected.